A central issue in immunology concerns the understanding of the functional interaction between H-2 coded antigens and neoantigens (i.e., viral, tumor, or minor-H). The problem has far-reaching implications in the mechanisms of immunity; the understanding of receptor specificity will shed light on T and B cell ontogeny, function, and pathology. Cytotoxic T lymphocytes (CTLs) directed against the major surface glycoprotein (G protein) of vesicular stomatitis virus or the hemagglutinin (HA) of influenza virus recognize the viral protein in an H-2 restricted fashion. These viral antigens and H-2 proteins can be purified and incorporated into synthetic phospholipid membranes (liposomes) which are capable of stimulating a secondary CTL response. Not only is this response H-2 restricted, but the magnitude of the response is dependent on the H-2 haplotype. It is the H-2Kk and H-2Dk systems which result in a weak anti-VSV G protein response whereas it is the H-2Kb which results in a weak anti-influenza response. The goal of this project is to identify and characterize associations which occur between these viral antigens and H-2 proteins in liposomal membranes and to compare these associations to the biological reactivity of these liposomes. Electron paramagnetic spectroscopy and fluorescence energy transfer will be used to quantitate the interactions between viral and H-2 proteins in the liposomes. In addition, we will quantitate the extent of association between these viral proteins and H-2 molecules in virus-infected cells (these cells are sensitive to lysis by anti-viral CTLs) by using spin-labeled monoclonal antibodies specific for the viral proteins and H-2 molecules. The long-term objective is to evaluate the molecular requirements for recognition of a determinant by the T cell receptor.